Lab website: http://genetics.bwh.harvard.edu/wiki/cassa

Research Overview

One of the most important problems in modern clinical and translational medicine is the analysis of genetic and genomic data. Healthy individuals carry genetic variants which may predispose them to a variety of both common and rare disorders, and there is a pressing need to distinguish between causal variants and those that are either incompletely penetrant or false positives. Dr. Cassa's research group develops methods to computationally assess the clinical impact of these genetic variants using previously unleveraged population health datasets and machine learning approaches.

About the Researcher

Christopher Cassa, PhD, is a graduate of the Harvard-MIT Division of Health Sciences and Technology program in Bioinformatics and Integrative Genomics. Dr. Cassa is an Assistant Professor of Medicine at Harvard Medical School, a research affiliate at Boston Children’s Hospital, a geneticist at Brigham and Women’s Hospital and a research affiliate at the Broad Institute.

Researcher Services

Researcher Areas

  • Computational Genomics

Research Departments

Research Divisions

PUBLICATIONS

Publications powered by Harvard Catalyst Profiles

  1. Weghorn D, Balick DJ, Cassa C, Kosmicki JA, Daly MJ, Beier DR, Sunyaev SR. Applicability of the mutation-selection balance model to population genetics of heterozygous protein-truncating variants in humans. Mol Biol Evol. 2019 Apr 19. View abstract
  2. Mohanty AK, Vuzman D, Francioli L, Cassa C, Toth-Petroczy A, Sunyaev S. novoCaller: a Bayesian network approach for de novo variant calling from pedigree and population sequence data. Bioinformatics. 2019 Apr 01; 35(7):1174-1180. View abstract
  3. Shen MW, Arbab M, Hsu JY, Worstell D, Culbertson SJ, Krabbe O, Cassa CA, Liu DR, Gifford DK, Sherwood RI. Author Correction: Predictable and precise template-free CRISPR editing of pathogenic variants. Nature. 2019 Mar; 567(7746):E1-E2. View abstract
  4. Cassa CA, Weghorn D, Balick DJ, Jordan DM, Nusinow D, Samocha KE, O'Donnell-Luria A, MacArthur DG, Daly MJ, Beier DR, Sunyaev SR. Reply to 'Selective effects of heterozygous protein-truncating variants'. Nat Genet. 2019 01; 51(1):3-4. View abstract
  5. Shen MW, Arbab M, Hsu JY, Worstell D, Culbertson SJ, Krabbe O, Cassa CA, Liu DR, Gifford DK, Sherwood RI. Predictable and precise template-free CRISPR editing of pathogenic variants. Nature. 2018 11; 563(7733):646-651. View abstract
  6. Haghighi A, Krier JB, Toth-Petroczy A, Cassa CA, Frank NY, Carmichael N, Fieg E, Bjonnes A, Mohanty A, Briere LC, Lincoln S, Lucia S, Gupta VA, Söylemez O, Sutti S, Kooshesh K, Qiu H, Fay CJ, Perroni V, Valerius J, Hanna M, Frank A, Ouahed J, Snapper SB, Pantazi A, Chopra SS, Leshchiner I, Stitziel NO, Feldweg A, Mannstadt M, Loscalzo J, Sweetser DA, Liao E, Stoler JM, Nowak CB, Sanchez-Lara PA, Klein OD, Perry H, Patsopoulos NA, Raychaudhuri S, Goessling W, Green RC, Seidman CE, MacRae CA, Sunyaev SR, Maas RL, Vuzman D. An integrated clinical program and crowdsourcing strategy for genomic sequencing and Mendelian disease gene discovery. NPJ Genom Med. 2018; 3:21. View abstract
  7. Cassa CA, Jordan DM, Adzhubei I, Sunyaev S. A literature review at genome scale: improving clinical variant assessment. Genet Med. 2018 09; 20(9):936-941. View abstract
  8. Cassa CA, Akle S, Jordan DM, Rosenfeld JA. When "N of 2" is not enough: integrating statistical and functional data in gene discovery. Cold Spring Harb Mol Case Stud. 2017 05; 3(3):a001099. View abstract
  9. Cassa CA, Weghorn D, Balick DJ, Jordan DM, Nusinow D, Samocha KE, O'Donnell-Luria A, MacArthur DG, Daly MJ, Beier DR, Sunyaev SR. Estimating the selective effects of heterozygous protein-truncating variants from human exome data. Nat Genet. 2017 May; 49(5):806-810. View abstract
  10. Lee VS, Halabi CM, Hoffman EP, Carmichael N, Leshchiner I, Lian CG, Bierhals AJ, Vuzman D, Mecham RP, Frank NY, Stitziel NO. Loss of function mutation in LOX causes thoracic aortic aneurysm and dissection in humans. Proc Natl Acad Sci U S A. 2016 08 02; 113(31):8759-64. View abstract
  11. Cassa CA, Smith SE, Docken W, Hoffman E, McLaughlin H, Chun S, Leshchiner I, Miraoui H, Raychaudhuri S, Frank NY, Wilson BJ, Sunyaev SR, Maas RL, Vuzman D. An argument for early genomic sequencing in atypical cases: a WISP3 variant leads to diagnosis of progressive pseudorheumatoid arthropathy of childhood. Rheumatology (Oxford). 2016 Mar; 55(3):586-9. View abstract
  12. Akle S, Chun S, Jordan DM, Cassa CA. Mitigating false-positive associations in rare disease gene discovery. Hum Mutat. 2015 Oct; 36(10):998-1003. View abstract
  13. Balick DJ, Do R, Cassa CA, Reich D, Sunyaev SR. Dominance of Deleterious Alleles Controls the Response to a Population Bottleneck. PLoS Genet. 2015 Aug; 11(8):e1005436. View abstract
  14. Jordan DM, Frangakis SG, Golzio C, Cassa CA, Kurtzberg J, Davis EE, Sunyaev SR, Katsanis N. Identification of cis-suppression of human disease mutations by comparative genomics. Nature. 2015 Aug 13; 524(7564):225-9. View abstract
  15. Chopra SS, Leshchiner I, Duzkale H, McLaughlin H, Giovanni M, Zhang C, Stitziel N, Fingeroth J, Joyce RM, Lebo M, Rehm H, Vuzman D, Maas R, Sunyaev SR, Murray M, Cassa CA. Inherited CHST11/MIR3922 deletion is associated with a novel recessive syndrome presenting with skeletal malformation and malignant lymphoproliferative disease. Mol Genet Genomic Med. 2015 Sep; 3(5):413-23. View abstract
  16. Brownstein CA, Beggs AH, Homer N, Merriman B, Yu TW, Flannery KC, DeChene ET, Towne MC, Savage SK, Price EN, Holm IA, Luquette LJ, Lyon E, Majzoub J, Neupert P, McCallie D, Szolovits P, Willard HF, Mendelsohn NJ, Temme R, Finkel RS, Yum SW, Medne L, Sunyaev SR, Adzhubey I, Cassa CA, de Bakker PI, Duzkale H, Dworzynski P, Fairbrother W, Francioli L, Funke BH, Giovanni MA, Handsaker RE, Lage K, Lebo MS, Lek M, Leshchiner I, MacArthur DG, McLaughlin HM, Murray MF, Pers TH, Polak PP, Raychaudhuri S, Rehm HL, Soemedi R, Stitziel NO, Vestecka S, Supper J, Gugenmus C, Klocke B, Hahn A, Schubach M, Menzel M, Biskup S, Freisinger P, Deng M, Braun M, Perner S, Smith RJ, Andorf JL, Huang J, Ryckman K, Sheffield VC, Stone EM, Bair T, Black-Ziegelbein EA, Braun TA, Darbro B, DeLuca AP, Kolbe DL, Scheetz TE, Shearer AE, Sompallae R, Wang K, Bassuk AG, Edens E, Mathews K, Moore SA, Shchelochkov OA, Trapane P, Bossler A, Campbell CA, Heusel JW, Kwitek A, Maga T, Panzer K, Wassink T, Van Daele D, Azaiez H, Booth K, Meyer N, Segal MM, Williams MS, Tromp G, White P, Corsmeier D, Fitzgerald-Butt S, Herman G, Lamb-Thrush D, McBride KL, Newsom D, Pierson CR, Rakowsky AT, Maver A, Lovrecic L, Palandacic A, Peterlin B, Torkamani A, Wedell A, Huss M, Alexeyenko A, Lindvall JM, Magnusson M, Nilsson D, Stranneheim H, Taylan F, Gilissen C, Hoischen A, van Bon B, Yntema H, Nelen M, Zhang W, Sager J, Zhang L, Blair K, Kural D, Cariaso M, Lennon GG, Javed A, Agrawal S, Ng PC, Sandhu KS, Krishna S, Veeramachaneni V, Isakov O, Halperin E, Friedman E, Shomron N, Glusman G, Roach JC, Caballero J, Cox HC, Mauldin D, Ament SA, Rowen L, Richards DR, San Lucas FA, Gonzalez-Garay ML, Caskey CT, Bai Y, Huang Y, Fang F, Zhang Y, Wang Z, Barrera J, Garcia-Lobo JM, González-Lamuño D, Llorca J, Rodriguez MC, Varela I, Reese MG, De La Vega FM, Kiruluta E, Cargill M, Hart RK, Sorenson JM, Lyon GJ, Stevenson DA, Bray BE, Moore BM, Eilbeck K, Yandell M, Zhao H, Hou L, Chen X, Yan X, Chen M, Li C, Yang C, Gunel M, Li P, Kong Y, Alexander AC, Albertyn ZI, Boycott KM, Bulman DE, Gordon PM, Innes AM, Knoppers BM, Majewski J, Marshall CR, Parboosingh JS, Sawyer SL, Samuels ME, Schwartzentruber J, Kohane IS, Margulies DM. An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge. Genome Biol. 2014 Mar 25; 15(3):R53. View abstract
  17. Cassa CA, Tong MY, Jordan DM. Large numbers of genetic variants considered to be pathogenic are common in asymptomatic individuals. Hum Mutat. 2013 Sep; 34(9):1216-20. View abstract
  18. Cassa CA, Chunara R, Mandl K, Brownstein JS. Twitter as a sentinel in emergency situations: lessons from the Boston marathon explosions. PLoS Curr. 2013 Jul 02; 5. View abstract
  19. Cassa CA, Miller RA, Mandl KD. A novel, privacy-preserving cryptographic approach for sharing sequencing data. J Am Med Inform Assoc. 2013 Jan 01; 20(1):69-76. View abstract
  20. Cassa CA, Savage SK, Taylor PL, Green RC, McGuire AL, Mandl KD. Disclosing pathogenic genetic variants to research participants: quantifying an emerging ethical responsibility. Genome Res. 2012 Mar; 22(3):421-8. View abstract
  21. Tong MY, Cassa CA, Kohane IS. Automated validation of genetic variants from large databases: ensuring that variant references refer to the same genomic locations. Bioinformatics. 2011 Mar 15; 27(6):891-3. View abstract
  22. Malin, B, Cassa C, Kantarcioglu M . Privacy-Aware Knowledge Discovery: Novel Applications and New Techniques, Chapman Hall / CRC Press. A Survey of Challenges and Solutions for Privacy in Clinical Genomics Data Mining. 2010. View abstract
  23. Cassa CA, Mandl KD. AMIA Annu Symp Proc. 2009. Risk of Re-Identification: Privacy Implications for Rare Mutation. 2009. View abstract
  24. Stoto, M. A., Dempsey, J. X., Baer, A., Cassa, C., Gibson, P. J., & Buehler, J. W. . Advances in Disease Surveillance. Expert Meeting on Privacy, Confidentiality, and Other Legal and Ethical Issues in Syndromic Surveillance. 2009; 7(2). View abstract
  25. Wieland SC, Cassa CA, Mandl KD, Berger B. Revealing the spatial distribution of a disease while preserving privacy. Proc Natl Acad Sci U S A. 2008 Nov 18; 105(46):17608-13. View abstract
  26. Cassa CA, Kenfield S, Daniel J, Mandl KD. The Massachusetts Health and Homeland Alert Network: a scalable and secure public health knowledge management and notification system. AMIA Annu Symp Proc. 2008 Nov 06; 893. View abstract
  27. Cassa CA, Wieland SC, Mandl KD. Re-identification of home addresses from spatial locations anonymized by Gaussian skew. Int J Health Geogr. 2008 Aug 12; 7:45. View abstract
  28. Cassa CA, Schmidt B, Kohane IS, Mandl KD. My sister's keeper?: genomic research and the identifiability of siblings. BMC Med Genomics. 2008 Jul 25; 1:32. View abstract
  29. Cassa, Christopher A. Privacy and identifiability in clinical research, personalized medicine, and public health surveillance. 2008. View abstract
  30. Cassa CA, Mandl KD. Multi-factor authentication using contents from disparate EHRs. AMIA Annu Symp Proc. 2007 Oct 11; 891. View abstract
  31. Brownstein JS, Cassa CA, Kohane IS, Mandl KD. An unsupervised classification method for inferring original case locations from low-resolution disease maps. Int J Health Geogr. 2006 Dec 08; 5:56. View abstract
  32. Brownstein JS, Cassa CA, Mandl KD. No place to hide--reverse identification of patients from published maps. N Engl J Med. 2006 Oct 19; 355(16):1741-2. View abstract
  33. Grannis S, Egg J, Cassa C, Olson K, Mandl K, Overhage J . Proc Symp 2006 Syndromic Surveillance Conf, Baltimore, MD. Evaluating the Performance of a Spatial Scan Statistic Using Simulated Outbreak Characteristics. 2006. View abstract
  34. Cassa CA, Grannis SJ, Overhage JM, Mandl KD. A context-sensitive approach to anonymizing spatial surveillance data: impact on outbreak detection. J Am Med Inform Assoc. 2006 Mar-Apr; 13(2):160-5. View abstract
  35. Cassa CA, Iancu K, Olson KL, Mandl KD. A software tool for creating simulated outbreaks to benchmark surveillance systems. BMC Med Inform Decis Mak. 2005 Jul 14; 5:22. View abstract
  36. Brownstein JS, Cassa CA, Kohane IS, Mandl KD. Reverse geocoding: concerns about patient confidentiality in the display of geospatial health data. AMIA Annu Symp Proc. 2005; 905. View abstract
  37. Grannis S, Mandl K, Olson K, Cassa C, Overhage JM . International Society of Disease Surveillance Annu Symp Proc. Boston, MA. Geographic Coordinate Transformation Methods to Reduce Privacy Risks Associated with Surveillance. 2004. View abstract
  38. Mandl KD, Reis B, Cassa C. Measuring outbreak-detection performance by using controlled feature set simulations. MMWR Suppl. 2004 Sep 24; 53:130-6. View abstract
  39. Cassa, Christopher A. Spatial outbreak detection analysis tool : a system to create sets of semi-synthetic geo-spatial clusters. 2004. View abstract